Application of the Intramolecular α-Amidoalkylation Reaction for the Synthesis of 3- and 1,3-Alkyl(aryl) 2-Formyltetrahydroisoquinolines

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• 1H-NMR spectra were measured on a Tesla BS 587A 80 MHz spectrometer. The data in δ ppm in CDCI3 (TMS) are as follows∗: 2a 1.11(d, 3H, J=6), 2.66–2.82(m, 2H, J=4), 4.21–4.50(m, 1H, J=7), 6.25–6.50(s, 1H, br.), 7.23(s, 5H), 8.00(s, 1H); 2b 3.05(d, 2H, J=7), 5.05–5.43(m, 1H, J=6), 6.30–6.60(s, 1H, br.), 7.00(s, 4H), 7.15(s, 6H), 7.88(s, 1H); 2c 3.08(d, 2H, J=7), 3.75(s, 3H), 3.83(s, 3H), 5.05–5. 45(m, 1H, J=8), 6. 12–6.38(s, 1H, br.), 6.68 (s, 1H), 6.75(s, 2H), 7.00–7.25 (m, 5H), 8.10(s, 1H); 2d 2.94(d, 2H, J=7), 3.70(s, 3H), 4.80–5.20(m, 1H, J=6), 6.30–6.50(s, 1H, br.), 6.77 (d, 2H, J=9), 7.20 (s, 5H), 7.75(d, 2H, J=9), 8.26, 8.34 (s, s, 1H); 2e 1.15(d, 3H), 2.67–2.80(m, 2H), 3.85 (s, 6H), 4.20–4.46(m, 1H, J=8), 5.50–5.75(s, 1H, br.), 6.72 (s, 3H), 8.08(s, 1H); 2f 3.00(d, 2H, J=7), 3.67(s, 3H), 3.80(s, 3H), 5.15–5.38(m, 1H, J=8), 6.05–6.30(s, 1H, br.), 6.42(s, 1H), 6.67(s, 2H), 7, 23(s, 5H), 8.10(s, 1H); 2g 2.98–3.20(m, 2H), 3.80(s, 6H), 3.95(s, 6H), 5.10–5.40 (m, 1H), 6.05–6.30(s, 1H, br.), 6.45(s, 2H), 6.60(s, 2H), 6.70(s, 2H), 8.00(s, 1H); 2h 2.90(d, 2H, J=7), 3.40 (s, 3H), 3.70(s, 6H), 4.90–5.20(m, 1H), 6.10–6.30 (s, 1H, br.), 6.72 (s, 4H), 7.15(s, 2H), 7.20(s, 1H), 7.95 (s, 1H); 6a1.23, 1.29(d, d, 3H, J=3), 2.55–2.85(m, 1H), 4.32(d, 2H, J=16), 5.12 (d, 2H, J=16), 7.15(s, 4H), 8.23, 8.25(s, s, 1H); 6b 3.29(d, 2H, J=5), 4.14(d, 2H, J=15), 5.00–5.12(m, 1H), 7.14(s, 2H), 7.20(s, 5H), 7.24(s, 2H), 8.34(s, 1H); 6c 3.36(d, 2H, J=5), 3.74(s, 3H), 3.82 (s, 3H), 4.20(d, 2H, J=14), 4.96–5.16(m, 1H), 6.64(s, 1H), 6.72(s, 1H), 7.18(s, 3H), 7.27(s, 2H), 8.32, 8.36(s, s, 1H); 6d 3.31(d, 2H, J=5), 3.71(s, 3H), 4.28(d, 2H, J=15), 4.95 5.17(m, 1H), 6.71(s, 1H), 6.74 (s, 2H), 7.02–7.25(m, 5H), 8.29, 8.34(s, s, 1H); 6e1.34 (d, d, 3H, J=6), 2.45–2.75 (m, 1H), 3.85(s, 6H), 4.32(d, 2H, J=14), 5.00(d, 2H, J=16), 6.57(s, 1H), 7.29(s, 1H), 8.24, 8.25(s, s, 1H); 6f 3.25 (d, 2H, J=6), 3.82(s, 3H), 3.90 (s, 3H), 4.20(d, 2H, J=14), 4.90–5.12(m, 1H), 6.55 (d, 1H, J=6), 6.70(d, 1H, J=6), 7.24 (s, 5H), 8.32, 8.38(s, s, 1H); 6g 3.25(d, 2H, J=5), 3.76 (s, 3H), 3.82(s, 6H), 3.86(s, 3H), 4.16(d, 2H, J=12), 4.99–5.27(m, 1H), 6.0(s, 1H), 6.56(s, 1H), 6.66(s, 1H), 6.72 (s, 2H), 8.31, 8.36(s, s, 1H); 6h 3.25(d, 2H, J=5), 3.75 (s, 3H), 3.85(s, 3H), 3.95(s, 3H), 4.10–4.25(m, 2H), 4.86–5.12(m, 1H), 6.50–6.85(m, 4H), 7.05–7.25(m, 2H), 8.25, 8.32(s, s, 1H); 6i 1.18(d, 3H, J=6), 1.28(d, 3H, J=6), 2.41–2.93(m, 4H), 3.77(s, 3H), 3.85, 3.88(s, 3H), 3.888(s, 3H), 3.92(s, 3H), 3.98–4.20(m, 2H), 5.66 (s, 2H), 6.63– 6.80(m, 4H), 7.25(s, 6H), 7.28(s, 4H), 8.38, 8.41, 8.46 (s, s, s, 2H); ∗The doubled signals are due to conformers, or a mixture of diastereomers.
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• The M.S. spectra were recorded on a JMS-D300 spectrometer and m/e (M+) are as follows: 2a 163 (C10H13NO,163.2); 2b 225 (C15H15NO, 225.3); 2c 285 (C17H19NO3, 285.3); 2d 255 (C16H17NO2, 255.3); 2e 223 (C12H17NO3, 223.3); 2f 285 (C17H19NO3, 285.3); 2g 345 (C19H23NO3, 345.4); 2h 315 (C19H21NO4, 345.4); 6a 175 (C11H13NO, 175.2); 6b 237 (C16H15NO, 237.3); 6c 297 (C18H19NO3, 297.4); 6d 267 (C17H17NO2, 267.3); 6e 235 (C13H17NO3, 235.3); 6f 297 (C18H19NO3, 297.4); 6g 357 (C20H23NO5, 357.4); 6h 327 (C19H21NO4, 327.4); 6i 311 (C19H21NO3, 311.4); 6j 373 (C24H23NO3, 373.4).
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• One of the diastereomers of 6i was separated by recrystallization from methanol; m.p. 167–168°C; H1-NMR (CDCI3/TMS), δ :1.18(d, 3H, J=6), 2.61–2.94 (m, 2H), 3.80(s, 3H), 3.91(s, 3H), 4.06–4.20(m, 1H), 5.68 (s, 1H), 6.63–6.72(m, 2H), 7.22(s, 5H), 8.38, 8.41, 8.47 (s, s, 1H);
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• 6j was separated to three diastereomers by column chromatography on a silica gel (70–230mesch,Merck). The first one was isolated at eluent a mixture of petroleum ether:ether (2:1) in a yield of 16%; crystals with m.p. 163–164°C. H1-NMR (CDCI3/TMS): 3.13(d, 2H, J=6), 3.80(s, 6H), 4.90(t, 1H, J=6), 5.65(s, 1H) 6.55(s, 1H), 6.73(s, 1H), 7.02–7.22(m, 5H), 7.25(s, 5H), 7.95, 8.25(s, s, 1H); The second diastereomer was isolated at eluent ether in a yield of 14%; crystals with m.p. 159–160°C. H1-NMR (CDCI3/TMS): 2.84–3.03 (m, 2H), 3.82(s, 3H), 3.94(s, 3H), 4.72(t, 1H, J=7), 5.28(s, 1H), 5.85(s, 1H), 6.55(s, 1H), 6.74–7.26 (m, 10H), 8.38(s, 1H); The last diastereomer of 6j was isolated with CH2CI2 in a yield of 13% as crystals with m.p. 152–153°C. H1-NMR (CDCI3/TMS): 3.02(d, 2H, J=7), 3.65, 3.70(s, s, 3H), 3.81, 3.90(s, s, 3H), 5.28–5. 37 (m, 1H), 6.42(s, 1H), 6.48(s, 1H), 6.76(s, 1H), 7.14–7.27 (m, 10H), 7.87, 8.12(s, s, 1H);
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